PROJECT SUMMARY Decision-making operates over vastly different temporal scales. Although perceiving a sound requires information gathered over a time span of just milliseconds, deciding whom to marry may require years. Decision- makers also change over time. As we age, our perceptual and motor processing abilities change but also our knowledge base, our motivations and our comfort with risk change, all factors that contribute to our decisions. Recent work indicates that older adults may rely more on heuristics to inform their decisions, compared to younger adults. Conversely, we recently discovered that people with Parkinson?s disease, one of several related neurodegenerative proteinopathies falling along a continuum of alpha-synuclein and tauopathy that includes Alzheimer?s disease and variants of these two diseases, are impaired in the use of previously learned information (priors or heuristics) to guide perceptual decisions. Together these results indicate that the ability to use prior information for decisions changes over the lifespan and with diseases associated with aging. It is unknown how the use of priors or heuristics for perceptual decision-making develops or changes over the lifespan. It is equally unknown how the ability to use heuristics for decision-making is impaired with aging or neurodegenerative disease. Therefore, we propose to develop a novel animal model of decision-making behavior over the lifespan to test the hypothesis that the use of heuristics for decision-making differs between young and old and those with age-related proteinopathy and neurodegeneration. The results of our proposed experiments will provide a timeline of decision-making changes in a novel animal model of aging in health and disease. The results will provide the groundwork for future experiments designed to unravel the neural circuitry and neuropharmacology underlying decision-making changes over the lifespan and with age-related proteinopathies along the synuclein- tauopahy continuum, including Alzheimer?s disease, Parkinson?s disease and variants of these diseases, and thus facilitate the development of novel treatments for cognitive impairment associated with these diseases.